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Fig. 1 Bioinformatic workflow to define the in-silico matrisome of Drosophila melanogaster. The databases FlyBase, DIOPT, and Ensembl were interrogated with the full list of human and mouse matrisome and matrisome-associated gene symbols. Selected InterPro domains, including domains characteristic of collagens, proteoglycans, ECM-affiliated proteins, and cuticle-binding proteins (see Supplementary Table 4) were used to identify ECM-domain-containing proteins in the reference proteome. The Gene Ontology annotations related to the ECM were then used to identify previously-annotated ECM components. Finally, selected published literature using proteomic and/or bioinformatic methods, as well as reviews on the subject, were searched to identify ECM proteins not identified by the orthology-based or protein-sequencing methods. These data were combined and manually curated to generate the first complete Drosophila matrisome. Hs, Homo sapiens; Mm, Mus musculus; Dm Drosophila melanogaster.